Histone Genes

Berdasco M, Ropero S, Setien F et al (2009) Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma. Proc Natl Acad Sci USA 106 21830-21835... 

The nucleus is surrounded by a nuclear membrane and contains chromatin, which is composed of deoxyribonucleic acid (DNA), wherein reside the genes, histones (basic protein), nuclear acidic protein, and one or more nucleoli which contain ribonucleic acid (RNA). The histones and DNA are organized into nucleosomes (see Chapter 7). It has been estimated that each nucleus contains 6.2 pg of DNA (Vendrely and Vendrely, 1956). The mitochondria have an inner and outer membrane and contain the pyruvate dehydrogenase multi enzyme... 

More subtle modes of action are also possible since the response to hormone receptor binding is complex and could be affected by chemical interference with receptor-related proteins, DNA methylation or histone acetylation. Dioxin (TCDD), for example, reduces the ability of the oestrogen-receptor complex to bind to the oestrogen response element of DNA, reducing gene transcription. ... 

Clock gene and transcription factor with histone acetyl-transferase (HAT) activity that (in complex with BMAL1) constitutes a positive limb of molecular circadian oscillators. 

Repression of genes is associated with reversal of this process under the control of histone deacetylases (HDACs). Deacetylation of histones increases the winding of DNA round histone residues, resulting in a dense chromatin structure and reduced access of transcription factors to their binding sites, thereby leading to repressed transcription of inflammatory genes. 

Histone acetylation is a reversible and covalent modification of histone proteins introduced at the e-amino groups of lysine residues. Histones and DNA form a complex - chromatin - which condenses DNA and controls gene activity. Current models interpret histone acetylation as a means to regulate chromatin activity. 

A model called histone code theory includes more aspects of chromatin regulation which have been identified. The histone code theory predicts that histone acetylation and other posttranslational histone modifications serve as binding sites for regulatory proteins which mediate processes like gene transcription upon recruitment (see Fig. 2b) [3]. In this context histone modifications can be understood as... 

Gallinari P, Di Marco S, Pallaro M et al (2007) HDACS, histone deacetylation and gene transcription from molecular biology to cancer therapeutics. Cell Res 17 195-211... 

Histone tails are the N-terminal regions of histones which reach outside the nucleosomes. They are not essential for the formation in of nucleosomes but are required for the formation of higher-order chromatin structures. The histone tails are also known to be heavily posttranslationally modified by acetylation, phosphorylation, methylation, etc. and are important for the regulation of gene activity. 

Small nuclear RNAs (snRNAs), a subset of these RNAs, are significantly involved in mRNA processing and gene regulation. Of the several snRNAs, Ul, U2, U4, U5, and U6 are involved in intron removal and the processing of hnRNA into mRNA (Chapter 37). The U7 snRNA may be involved in production of the correct 3 ends of histone mRNA—which lacks a poly(A) tail. The U4 and U6 snRNAs may also be required for poly(A) processing. 

Acetylation of histones H3 and H4 is associated with the activation or inactivation of gene transcription (Chapter 37). 

Methylation of histones is correlated with activation and repression of gene transcription. 

Some of this differential expression is achieved by having different regions of chromatin available for transcription in cells from various tissues. For example, the DNA containing the P-globin gene cluster is in active chromatin in the reticulocyte but in inactive chromatin in muscle cells. All the factors involved in the determination of active chromatin have not been elucidated. The presence of nucleosomes and of complexes of histones and DNA (see Chapter 36) certainly provides a barrier against the ready association of transcription fac-... 

The cis-acting elements that decrease or repress the expression of specific genes have also been identified. Because fewet of these elements have been smdied, it is not possible to fotmulate genetalizations about their mechanism of action—though again, as for gene activation, chromatin level covalent modifications of histones and other proteins by (repressor)-recruited multisubunit corepressors have been imphcated. 

Review] [67 refs]. Clin Diagn Lab Immunol 7 719-723 Bodnar RJ (2007) Endogenous opiates and behavior 2006. Peptides 28 2435-2513 Boekhoudt GH, Guo Z, Beresford GW, Boss JM (2003) Communication between NF-kappa B and Spl controls histone acetylation within the proximal promoter of the monocyte chemoattractant protein 1 gene. J Immunol 170 4139-4147... 

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